2. Seen in less than 2% of healthy term infants and in 30% to 95% of healthy preterm infants more than 24 hours of age.

3. Not accompanied by cyanosis or changes in heart rate.

4. Episodes of periodic breathing in the preterm infant decrease significantly by 39 to 41 weeks of postmenstrual age (Miller et al., 2010).

5. Studies do not support a link between periodic breathing and significant apnea or sudden infant death syndrome (SIDS) (Miller et al., 2010).

B. Apnea.

2. Exposure to stimulation and/or oxygen will usually induce spontaneous respiratory effort.

B. Secondary apnea.

2. Infant will not respond to stimulation and will require more vigorous resuscitation.

3. For each minute in secondary apnea before resuscitation, there is a 2-minute delay before gasping is reestablished and another 2 minutes before the onset of regular respirations.

2. Cause of central apnea in the preterm infant is not fully understood.

3. Contributing factors are thought to include the following:

b. Diaphragmatic fatigue.

c. Immature, paradoxic response of neonate to hypoxia and hypercapnia.

d. Altered levels of local neurotransmitters in the brainstem region of the central nervous system (CNS).

4. Fifteen percent of apnea episodes are central in origin.

2. Fifty percent to 60% of neonatal apnea episodes are mixed.

F. Idiopathic apnea, or apnea of prematurity.

2. Not necessarily associated with the presence of periodic breathing.

3. Recurrent apnea seen in preterm infants who show no other abnormalities.

4. Onset within the first week of life, usually at 24 to 48 hours. If not present within the first week of life, will usually not appear unless later illness develops. If mechanically ventilated, apnea may not present until postextubation.

5. More likely to be obstructive than central in the first 2 days of life.

6. Episodes of apnea cease by term in 95% of infants; may persist longer in infants born at less than 28 weeks of gestational age (Scott et al., 2011).

b. Decreased number of synapses, and

c. Decreased dendritic arborization.

2. Thermal receptors in the trigeminal area of the face produce an apneic response to stimulation by a cold or hot gas mixture.

D. Mechanoreceptors.

b. Hering–Breuer reflex.

(2) Lung inflation initiates inhibitory impulses that terminate inspiration and prolong expiratory time.

(3) Mechanoreceptors are very active in the neonate but rarely seen in the adult.

2. Pharyngeal collapse and airway obstruction are produced by negative pharyngeal pressure generated during inspiration.

2. Pulmonary irritant receptors can produce an apneic response to direct bronchial stimulation.

2. Respiratory depression occurs predominantly in rapid eye movement (REM) or transitional sleep.

(2) Variability of respiratory rhythmicity is seen in active sleep.

b. May be related to paradoxical respirations in which chest wall movements are out of phase, resulting in rib cage collapse with abdominal expansion during inspiration. This would lead to a decrease in lung volume and functional residual capacity.

B. Hypoxia.

C. Respiratory disorders.

2. Pneumonia.

3. Aspiration.

4. Acidosis.

5. Airway obstruction.

6. Pneumothorax.

7. Atelectasis.

8. Pulmonary hemorrhage.

9. Postextubation status.

10. Congenital anomalies of the upper airway.

D. Cardiovascular disorders.

2. Arrhythmias.

3. Congestive heart failure.

4. Patent ductus arteriosus.

E. Infection.

2. Pneumonia.

3. Meningitis.

4. Viral infections.

5. Necrotizing enterocolitis.

F. CNS disorders.

2. Seizures.

3. Asphyxia.

4. Intracranial hemorrhage.

5. Kernicterus.

6. Tumors.

G. Drugs.

b. Analgesics.

c. Anesthesia.

d. β-Blocker antihypertensive agents.

e. Magnesium sulfate.

2. Neonatal drugs.

b. Cardiovascular drugs: prostaglandin E₁.

c. Narcotics/analgesics.

(2) Morphine.

(3) Midazolam hydrochloride.

(4) Lorazepam.

H. Metabolic disorders.

2. Hypoglycemia.

3. Hypomagnesemia.

4. Hyponatremia.

5. Acidosis.

6. Hyperammonemia.

I. Hematopoietic disorders.

2. Anemia.

J. Reflex stimulation.

2. Hypothermia.

3. Hyperthermia.

4. Elevated environmental temperature.

5. Feeding.

6. Stooling.

7. Painful stimuli.

b. Fetal hypoxia, trauma.

2. Neonatal risk factors.

b. Cardiorespiratory disease.

c. Metabolic abnormalities.

d. Temperature instability.

e. Infection.

f. Environmental causes.

g. CNS disorders.

B. Physical examination. A complete physical and neurologic examination should be performed. Evaluate for congenital malformations, especially those involving the airway. Evaluate for signs of respiratory distress and heart disease. Abnormal behavior, tone, or posturing may be associated with a neurologic focus. An abdominal examination should be performed, which may reveal symptoms related to obstruction, infection, necrotizing enterocolitis, or congestive heart failure.

C. Documentation of apnea episodes. A record of apneic episodes should be maintained as part of the infant’s record. This allows the caregiver to determine a pattern, if any, to the apnea. It may also provide information about precipitating events or specific events associated with the apnea. Information documented should include the following:

2. Time of apnea episode and any relation to feeding, activity, stooling, sleep, or procedures.

3. Infant’s position: prone or supine, with head of bed elevated or flat.

4. Associated bradycardia/heart rate.

5. Associated color change and/or oxygen desaturation.

6. Type of stimulation required to resolve the episode:

b. Gentle tactile stimulation.

c. Vigorous tactile stimulation.

d. Oxygen.

e. Bag-and-mask ventilation.

D. Laboratory evaluation.

b. Blood gases.

c. Serum glucose, electrolytes, calcium, magnesium.

d. Blood culture, lumbar puncture for evaluation of cerebrospinal fluid, and urine culture.

2. Extensive laboratory evaluation for less common causes of apnea.

b. Urine collection for detection of amino acids and organic acids.

c. Serum ammonia.

d. State screen and expanded neonatal screen for metabolic disease.

E. Other.

2. Electroencephalogram: may confirm suspected seizures.

3. Chest x-ray: may demonstrate respiratory or cardiac abnormalities.

4. Cranial ultrasound, computed tomography, or magnetic resonance imaging: may demonstrate structural abnormalities or hemorrhages.

5. Barium swallow and pH study: to evaluate pharyngeal structure and function or gastroesophageal reflux.

6. Pneumogram.

b. No predictive value for SIDS; recording monitors are as effective at detecting apnea over a prolonged period.

B. Provide needed medical or surgical intervention.

C. Maintain environmental temperature at the low end of the neutral thermal zone.

D. Avoid triggering reflexes:

2. Hot or cold to the face.

3. Sudden gastric distention.

2. Complicates gavage feedings and may increase risk of aspiration. Increases risk of air leak.

J. Pharmacologic therapy.

(2) Increased ventilatory response to carbon dioxide.

(3) Increased oxygenation.

(4) Increased minute ventilation (theophylline).

(5) Stabilization of oscillations in breathing (theophylline).

(6) Improved diaphragmatic contractility.

(7) Relaxation of bronchial smooth muscle (theophylline).

(8) CNS excitation.

(9) Increased respiratory drive.

(10) Increased respiratory muscle activity.

(11) Increased skeletal muscle activity.

b. Pharmacokinetics.

(2) Half-life of caffeine is approximately 100 hours.

(3) Both theophylline and caffeine are rapidly absorbed intravenously. Oral absorption of caffeine is rapid, and oral absorption of theophylline is variable.

(4) Metabolism of caffeine and theophylline takes place in the liver. This is slower in the neonate than in the adult.

(5) Theophylline is metabolized to caffeine by a metabolic pathway unique to the preterm infant.

(6) Serum concentrations must be checked to avoid toxic levels.

c. Dosage:

(b) Loading dose: 5 to 8 mg/kg.

(c) Maintenance dose: 2 to 6 mg/kg/day divided every 8 to 12 hours.

(d) Therapeutic level: 5 to 15 mcg/mL.

(2) Caffeine.

(b) Loading dose: 10 mg/kg, caffeine base; 20 mg/kg, caffeine citrate.

(2) Theophylline: tachycardia, cardiac dysrhythmias, seizures, jitteriness, feeding intolerance, gastroesophageal reflux, dehydration, hyperglycemia, and hypotension.

e. Caffeine versus theophylline.

(2) Theophylline causes a more rapid and sustained tachycardia.

(3) Caffeine diffuses more rapidly in the CNS.

(4) Caffeine is given only once a day.

(5) Caffeine has a wider therapeutic index.

(6) Caffeine may be effective in apnea not responsive to theophylline and vice versa.

(7) Caffeine has a longer half-life, resulting in smaller changes in its plasma concentration.

b. Mechanism of action thought to be stimulation of the peripheral chemoreceptors at low doses (0.5 mg/kg/hr) and of the CNS at higher doses.

c. Increases minute ventilation, tidal volume, and mean inspiratory flow and decreases PCO₂ (Dani et al., 2006).

d. Pharmacokinetics.

(2) Steady-state levels are reached within 24 hours.

e. Dosage.

(2) Loading dose: 2.5 to 3 mg/kg followed by (3).

(3) Continuous infusion of 1/mg/kg/hr, titrate to lowest effective dose. Maximum 2.5 mg/kg/hr.

(4) Controversy exists over therapeutic and toxic plasma levels. Guidelines include the following:

(b) Toxic level: 5 mg/L. Levels greater than 3.5 mg/L may produce side effects.

f. Side effects.

(2) Hypertension, tachycardia, and increased cardiac output.

(3) Increased work of breathing resulting from respiratory stimulation, consequent increased oxygen consumption and carbon dioxide production, and increased tidal volume and respiratory rate.

(4) Increased risk of intraventricular hemorrhage if used in the first few days of life.

g. Contraindication: use in newborn infant not routinely recommended because preparation contains benzyl alcohol.

(2) Cumulative doses might be toxic for the liver, kidney, or brain.

2. A survivor of an apparent life-threatening event defined as apnea, cyanosis, altered muscle tone, choking, or gagging.

3. Sibling death due to SIDS.

4. Tracheostomy, mechanically supported ventilation.

5. A sleep apnea syndrome caused by a neurologic disorder, periodic breathing, upper airway abnormality, or idiopathic syndromes.

6. Other conditions of ill or high-risk infants, as determined on an individual basis.

C. Home monitoring is not indicated in prevention of SIDS in symptom-free, healthy infants.

D. Monitoring technology.

b. A small electric current passes between the electrodes. The impedance to this current is measured as the chest wall diameter changes. The monitor senses this change and equates it with respiration.

c. Electrocardiograph reads cardiac activity.

d. High and low limits for respirations and heart rate are set by the clinician.

e. Monitor is compact and portable, weighing less than 5 pounds. A battery pack is available for use outside the home.

2. Technical problems include artifacts from signal interference, false alarms caused by shallow breathing, and the monitor’s inability to detect obstructive apnea. Incorrect placement of leads can result in false alarms as well.

3. Advances in technology allow recording of home monitor events for evaluation by the clinician.

b. True events can be distinguished from false alarms.

c. Fewer rehospitalizations are needed.

d. Recording is as sensitive as a pneumogram for evaluating whether monitoring can be discontinued.

e. Fewer monitor days are needed for infants without events.

E. Follow-up care.

2. Family and other caregivers of the infant are trained in cardiopulmonary resuscitation before hospital discharge. Thorough education in use of the monitor is also provided before discharge.

3. Care includes close telephone contact—within 24 hours after discharge and every week to 2 weeks afterward as needed.

4. Visiting nurse makes home visit within the first week and then as needed.

5. A team member is available 24 hours a day for answering questions and solving problems. Equipment company representative is available as needed for problems and information.

6. Home follow-up does not replace clinic visits.